The objective of this proposal is to further exploit the novel chemistry and behavior of a new class of Tc-99m labeled fatty acid derivatives developed by Biostream as markers of myocardial fatty acid metabolism. Fatty acids are the primary source of energy for heart muscle under normal conditions of blood flow and oxygen delivery. When blood flow is diminished (ischemic), the heart lacks an adequate supply of oxygen to utilize fatty acids efficiently. To compensate, the heart immediately shifts from fatty acid metabolism to glucose metabolism. This is the basis for the ability of BMIPP, an I-23-labeled fatty acid analog currently marketed in Japan, to detect ischemic myocardium at rest. The proposed research seeks to determine the optimal structure for this new class of compound by screening a series of new analogs for heart uptake and retention in rats. Mechanistic evaluations will be performed on a smaller series of lead compounds using genetically engineered knock-out mice that are lacking the CD36 protein known to be responsible for fatty acid transport into the myocardium. New chelate technology will also be employed in an attempt to optimize further this new class of promising radiopharmaceuticals. PROPOSED COMMERCIAL APPLICATIONS: More than 40% of ER chest pain patients (ca. 3 million annually) are admitted to hospitals unnecessarily at an estimated cost of $10-$13 billion per year. Fatty acid analogs radiolabeled with Tc-99m present a novel solution to the triage of the chest pain patient, potentially offering both cost savings to the overall heath care system as well as significant commercial potential.